This NIDA P30 Center supplies the resources needed to apply cutting-edge genomic, proteomic, and bioinformatic technologies to the study of chronic viral infections that are a direct consequence of drug abuse and addiction. Over the past four years, our emphasis has been on hepatitis C virus (HCV) infection and its impact on liver function. In this competitive renewal, we propose to augment our work on HCV with an increased emphasis on AIDS and the intravenous drug abuse population. The Center's unifying theme is to integrate the use of global gene expression and protein profiling technologies to develop a detailed understanding of the host response to virus infection and the molecular mechanisms underlying the progression from chronic HCV infection to end-stage liver disease. To achieve this goal, we have brought together a diverse group of NIH-funded investigators, from basic science and clinical medicine, with combined expertise in virology, immunology, liver disease and transplantation, genomics, proteomics, bioinformatics, biostatistics, and technology development; this includes more than 20 key personnel and over 20 other significant contributors from over a dozen academic institutions and three corporations. This remarkable confluence of basic science and clinical medicine, together with genomic, proteomic, and information technologies, represents an unparalleled opportunity to make advances in our understanding HCV-associated liver disease, AIDS, and HCV/HIV-1 dual infection. The Center consists of three scientific Cores and an Administrative Core, which oversees all aspects of the Center. The Functional Genomics & Virology Core provides the biological samples used for our analyses, which include serial liver biopsies from patients with recurrent HCV after liver transplantation, biopsies from patients with HCV-associated liver disease, and liver biopsies from HCV-infected intravenous drug abusers who are undergoing methadone treatment. AIDS-related studies include the analysis of liver biopsies from patients co-infected with HCV and HIV-1 and from a nonhuman primate model of AIDS. The Proteomics Core is located at Pacific Northwest National Laboratory and provides the Center with world-class mass spectrometry instrumentation and state-of-the-art technology development. The Bioinformatics & Biostatistics Core provides the essential functions of data management, analysis, statistical evaluation, and data sharing and dissemination.